The Prevalence of Metabolic Acidosis in Patients with Different Stages of Chronic Kidney Disease: Single-Centre Study.

BACKGROUND: Metabolic acidosis (MA) is one of the most common consequences of CKD. MA is also a risk factor of CKD progression and increased mortality in these patients. AIM: The aim of this retrospective, cross-sectional study was to assess the prevalence of MA in different stages of CKD and renal replacement therapy (RRT) modalities - haemodialysis (HD) and peritoneal dialysis (PD). Additionally, the relationship between the prevalence of MA and aetiology of kidney disease was analysed. METHODS: One thousand five patients in different stages of CKD, or modalities of RRT were enrolled into this single-centre cross-sectional study. Forty-one patients were ruled out because of oral bicarbonate supplementation. In the remaining 964 patients (698 CKD stages 1-5, 226 HD, 40 PD), venous blood HCO3- concentration, as well as serum Cr and urea concentrations were assessed. MA was diagnosed when blood HCO3- concentration was below 22 mmol/L. RESULTS: The prevalence of MA increased among all stages of CKD. Patients on HD had lower prevalence of MA in comparison with CKD 5 patients with no RRT (38.5 vs. 56.0%; p = 0.02) In PD patients, the prevalence of MA was significantly lower than in HD patients (2.5 vs. 38.5%; p < 0.001). In the whole study group, there were no significant differences in the prevalence of MA between different aetiologies of CKD (glomerulonephritis 24%, hypertension 23%, diabetes 25%, and tubule-interstitial diseases 24%). Also, when only patients in stages CKD 3-5 were compared, no significant differences in the prevalence of acidosis were found (glomerulonephritis 28%, hypertension 22%, diabetes 24%, and tubule-interstitial 21%). CONCLUSIONS: (1) MA is more frequent in patients with more advanced stages of CKD. (2) RRT reduces the prevalence of MA. (3) In PD patients, MA is rare. (4) Aetiology of CKD seems not to have a significant impact on MA prevalence.

Plasma marinobufagenin immunoreactivity in patients with chronic kidney disease: a case control study.

Experimental data have shown increased plasma levels of marinobufagenin in kidney failure. In this case-controlled retrospective analysis, we evaluated plasma marinobufagenin immunoreactivity in hemodialysis patients compared with subjects with normal kidney function. Sixty-eight adult hemodialysis patients with chronic kidney disease (34 females and 34 males) as well as 68 age-, gender-, and blood pressure-matched subjects without chronic kidney disease were enrolled. Patients on stable hemodialysis regimen for at least 3 mo before the study were included. Exclusion criteria were: age <18 yr, severe liver or heart insufficiency, and overhydration. Subjects without chronic kidney disease must have had an estimated glomerular filtration rate ≥60 ml·min-1·1.72 m-2 according to the Modification of Diet in Renal Disease formula. Plasma marinobufagenin immunoreactivity was significantly ( P < 0.001) higher in hemodialysis patients (1.66 ± 1.13 nmol/l) compared with subjects with normal kidney function (0.46 ± 0.23). In hemodialysis patients, plasma marinobufagenin immunoreactivity was higher in men compared with women. A significant positive correlation has been found between plasma marinobufagenin immunoreactivity and serum NT-proBNP, NT-proANP, or aldosterone concentrations in all analyzed subjects. In hemodialyzed patients with plasma marinobufagenin immunoreactivity above median value 5-yr, all-cause mortality was higher compared with those with plasma marinobufagenin concentration below median. We have shown that plasma marinobufagenin immunoreactivity is increased in patients with end-stage kidney failure treated with hemodialysis parallel to the increase in serum NT-proBNP, NT-proANP, and aldosterone concentrations. Higher marinobufagenin immunoreactivity has been associated with worse survival in hemodialyzed patients.

Different Relevance of Peripheral, Central or Nighttime Blood Pressure Measurements in the Prediction of Chronic Kidney Disease Progression in Patients with Mild or No-Proteinuria.

BACKGROUND/AIMS: Arterial hypertension is one of the leading factors aggravating the course of chronic kidney disease (CKD). It seems that the novel parameters used in the assessment of the blood pressure (BP) load (i.e. central blood pressure, nighttime blood pressure) may be more precise in predicting the cardiovascular risk and the progression of CKD in comparison with the traditional peripheral blood pressure measurements in the office conditions. The aim of the study was to assess the impact of the central, or nighttime blood pressure on the progression of CKD in patients with mild or no-proteinuria (autosomal, dominant polycystic kidney disease or IgA nephropathy). METHODS: In each of the enrolled 46 patients with CKD stage 3 or 4, serum creatinine concentration was assessed, eGFR (MDRD) was calculated, also central blood pressure and pulse wave velocity (PWV) was assessed and the 24-hour ambulatory blood pressure monitoring (ABPM) was conducted at the beginning of the study and then repeated after one-year observation period. RESULTS: During the observation period mean eGFR decreased from 44.1 (33.2-50.6) mL/min to 36.7 (29.7-46.3) mL/min. No significant differences were observed in the peripheral blood pressure or central blood pressure parameters. After one-year observation period the values of diastolic blood pressure dipping during the night significantly decreased from 16 (13-19) mmHg to 12 (10-15) mmHg; p< 0.05. The values of systolic dipping during the night or the mean BP values recorded in ABPM did not change significantly. Additionally, no significant differences in the PWV values were found. In the multivariate regression model the change of serum creatinine concentration was explained by the initial diastolic dipping values. CONCLUSION: 1. In patients with CKD stages 3 or 4 and mild or no- proteinuria, peripheral and central blood pressure did not change significantly during a one-year observation period despite the significant decline of eGFR and seems not to participate in the CKD progression. 2. Reduced magnitude of the diastolic dipping, which reflects the increase of diastolic blood pressure load during the nighttime, may play an important role in the pathogenesis of deterioration of kidney function in these patients.

Changes of Serum Total and Free Testosterone Concentrations in Male Chronic Hemodialysis Patients with Secondary Hyperparathyroidism in Response to Cinacalcet Treatment.

BACKGROUND/AIMS: Calcium sensing receptor (CaSR) is expressed, among others also in testis. Cinacalcet binds to the CaSR, increases sensitivity of CaSR to serum calcium and is used in the treatment of secondary hyperparathyroidism (sHPT) in chronic hemodialysis patients (HDP). In most of male HDP, serum testosterone concentration is lower than in healthy males. The aim of this study was to assess the influence of six-month treatment with cinacalcet on the serum total and free testosterone concentration in male HDP with sHPT. METHODS: 38 male, hemodialysed CKD patients with sHPT (PTH>300 pg/ml) were enrolled into the study. In each patient serum PTH, total testosterone (TT) and free testosterone (FT) concentrations were assessed before the first dose of cinacalcet and then after 3 and 6 months of treatment. The results are presented as means with 95% confidence interval. RESULTS: In 33 patients who completed the study cinacalcet treatment caused significant decrease of serum PTH from 1143 pg/ml (828 - 1458 pg/ml) at the baseline, to 809 pg/ml (487 - 1132 pg/ml) after 3 month of treatment (p = 0.002), and to 607 pg/ml (281 - 934 pg/ml; p < 0.0001) after 6 months of treatment. Serum TT concentration also decreased from 4.95 ng/ml (4.23 - 5.67 ng/ml) to 4.45 ng/ml (3.85 - 5.06 ng/ml) and to 4.39 ng/ml (3.75 - 5.03 ng/ml), respectively (p for trend = 0.009). Moreover, serum FT concentration decreased from 6.95 pg/ml (5.54 - 8.36 pg/ml) to 5.98 pg/ml (5.00-6.94 pg/ml); p = 0.14 and to 5.60 pg/ml (4.63 - 6.57 pg/ml); p = 0.034, respectively (p for trend = 0.012). CONCLUSION: Treatment with cinacalcet decreases serum total and free testosterone concentration in male hemodialysed patients with chronic kidney disease and secondary hyperparathyroidism.

Serum Anti-Müllerian Hormone Concentration in Young Women with Chronic Kidney Disease on Hemodialysis, and After Successful Kidney Transplantation.

BACKGROUND/AIMS: In women with chronic kidney disease (CKD) fertility abnormalities occur frequently. Anti-Müllerian hormone (AMH) inhibits excessive recruitment of primordial follicles. The aim of the study was to evaluate the serum AMH concentration in women on hemodialysis and after kidney transplantation (KTx). METHODS: 46 hemodialysed women and 14 with CKD about to undergo kidney transplantation were enrolled into the study. The control group consisted of 40 healthy women. In all subjects serum concentration of AMH was determined (in chronic hemodialysis women and in control group once, and in women after KTx immediately before surgery, and 3 times after the transplantation). RESULTS: Serum AMH concentration in hemodialysed women and in the control group did not differ significantly, while in hemodialysed women with regular menstrual cycles it was significantly lower than in the control group: 2.20 (1.08-3.55ng/ml) and 3.30 (1.80-6.10ng/ml) respectively, (p=0.02). In the KTx group, a significant decrease in serum AMH concentration was found from 3.30ng/ml (2.20-6.50ng/ml) at baseline to 1.90ng/ml (1.30-2.40ng/ml) at 6 months after KTx (p=0.007). CONCLUSIONS: 1. Significantly lower serum AMH concentration was found in the regularly menstruating CKD women on hemodialysis in comparison with the healthy controls. 2. Serum AMH decreased significantly after successful KTx.

Treatment with cinacalcet increases plasma sclerostin concentration in hemodialysis patients with secondary hyperparathyroidism.

BACKGROUND: Sclerostin is a paracrine acting factor, which is expressed in the osteocytes and articular chondrocytes. Sclerostin decreases the osteoblast-related bone formation through the inhibition of the Wnt/ß-catenin pathway. Osteocytes also express the Calcium sensing receptor which is a target for cinacalcet. The aim of this study was to assess the influence of six-month cinacalcet treatment on plasma sclerostin concentration in hemodialysed patients with secondary hyperparathyroidism (sHPT). METHODS: In 58 hemodialysed patients with sHPT (PTH > 300 pg/ml) plasma sclerostin and serum PTH, calcium and phosphate concentrations were assessed before the first dose of cinacalcet and after 3 and 6 months of treatment. RESULTS: Serum PTH concentration decreased after 3 and 6 month of treatment from 1138 (931-1345) pg/ml to 772 (551-992) pg/ml and to 635 (430-839) pg/ml, respectively. Mean serum calcium and phosphate concentrations remained stable. Plasma sclerostin concentration increased after 3 and 6 months of treatment from 1.66 (1.35-1.96) ng/ml, to 1.77 (1.43-2.12) ng/ml and to 1.87 (1.50-2.25) ng/ml, respectively. In 42 patients with cinacalcet induced serum PTH decrease plasma sclerostin concentration increased after 3 and 6 months of treatment from 1.51 (1.19-1.84) ng/ml to 1.59 (1.29-1.89) ng/ml and to 1.75 (1.42-2.01) ng/ml, respectively. Contrary, in the 16 patients without cinacalcet induced serum PTH decrease plasma sclerostin concentration was stable. Plasma sclerostin concentrations correlated inversely with serum PTH concentrations at the baseline and also after 6 months of treatment. CONCLUSIONS: 1. In hemodialysed patients with secondary hyperparathyroidism treatment with cinacalcet increases plasma sclerostin concentration 2. This effect seems to be related to decrease of serum PTH concentration.

TREATMENT WITH CINACALCET INCREASES PLASMA ADIPONECTIN CONCENTRATION IN HEMODIALYZED PATIENTS WITH CHRONIC KIDNEY DISEASE AND SECONDARY HYPERPARATHYROIDISM.

OBJECTIVE: Cinacalcet increases calcium-sensing receptor (CaSR) sensitivity to serum calcium. CaSR is expressed by adipocytes, and adiponectin is an adipokine with antiatherogenic and insulin-sensitizing properties. The aim of this study was to assess the influence of a 3-month cinacalcet regimen on plasma adiponectin concentration in hemodialyzed patients (HDP) with chronic kidney disease (CKD) and secondary hyperparathyroidism (sHPT). METHODS: Plasma adiponectin, advanced oxidation protein products (AOPP), serum interleukin-6 (IL-6) and C-reactive protein (CRP) concentrations were assessed in 65 HDP with sHPT treated with cinacalcet (30-120 mg/day) before the first dose and after 3 months of treatment. RESULTS: There was a significant decrease in serum parathyroid hormone (PTH) concentration: from 1,089 (891-1,286) pg/mL to 775 (574-976) pg/mL after 3 months of treatment (P<.0001). The treatment was associated with a significant (P = .048) increase in plasma adiponectin concentration from 16.9 (14.4-19.5) µg/mL to 17.8 (15.0-20.6) µg/mL. Significant (P = .03) reduction of plasma AOPP concentration was observed from 186.7 (156.7-216.7) pg/mL to 162.6 (141.2-183.9) pg/mL. CONCLUSIONS: A 3-month cinacalcet regimen increased plasma adiponectin concentrations in HDP with sHPT. Increased adiponectinemia in these patients may be related to reduced oxidative stress.

Cinacalcet treatment decreases plasma fibroblast growth factor 23 concentration in haemodialysed patients with chronic kidney disease and secondary hyperparathyroidism.

OBJECTIVE: Recent clinical studies suggest that fibroblast growth factor 23 (FGF23) is important in the pathogenesis of calcium-phosphate abnormalities in patients with chronic kidney disease and that increased plasma FGF23 concentration is a cardiovascular risk factor in these patients. The aim of this prospective, single-arm, open-label clinical study was to assess the influence of 6-month cinacalcet treatment on plasma FGF23 concentration in haemodialysed patients with secondary hyperparathyroidism (sHPT). DESIGN, PATIENTS AND MEASUREMENTS: In 58 haemodialysed patients with sHPT (parathormone PTH > 300 ng/l), serum PTH, FGF23, calcium and phosphate concentrations were assessed before the first dose of cinacalcet and after 3 and 6 months of treatment. RESULTS: Serum PTH concentration decreased significantly after 3 and 6 months of treatment, and the mean serum calcium and phosphate concentrations remained stable during the treatment period. Plasma FGF23 concentration (geometric mean with 95% confidence index) decreased after 3 and 6 months of treatment from 354 (261-481) ng/l to 295 (204-428) ng/l; P = 0·099 and to 183 (117-285) ng/l; P = 0·015, respectively. FGF23 concentration decreased in 52% of patients. In multivariate regression analysis, plasma FGF23 concentration changes were explained by the changes in serum phosphate, but not by serum PTH or calcium changes or by the dose of cinacalcet. CONCLUSIONS: 1. Cinacalcet treatment decreases plasma FGF23 concentration in haemodialysed patients with secondary hyperparathyroidism. 2. The decrease in plasma FGF23 concentration seems to be related to the decrease in serum phosphate concentration.

The odontogenic-related microinflammation in patients with chronic kidney disease.

OBJECTIVES: This study estimated plasma levels of interleukin IL-1ß, IL-6, tumour necrosis factor-α (TNF-α), interferon-γ (INF-γ) in chronic kidney disease (CKD) patients with a single odontogenic pathology. MATERIAL AND METHODS: Forty-nine selected adult CKD patients with single odontogenic pathology based on clinical and X-ray examination: patients after proper root canal treatment, without periapical lesions (n = 12), with pulp necrosis (n = 7), with asymptomatic periapical lesions (n = 22), with periodontal disease (n = 8), and 14 with healthy teeth were enrolled. Patients with coexisting different dental pathologies and the evidence of other infection were excluded. In all patients plasma concentrations of CRP, IL-1ß, IL-6, TNF-α, and INF-γ were measured. RESULTS: Patients with periodontitis were characterized by increased concentrations of IL-6 and TNF-α. Those with pulp necrosis had significantly more frequently serum CRP level over 2 mg/L and presented significantly elevated IL-6, but decreased TNF-α concentration than in the subjects with healthy teeth. In patients with periapical lesions and patients after root canal therapy, the concentrations of cytokines did not indicate for the systemic inflammation. CONCLUSIONS: Periodontitis and pulp necrosis are important sources of systemic microinflammation in CKD patients. Plasma concentrations of IL-6 and TNF-α appear to be more sensitive markers of odontogenic inflammation in CKD patients than CRP.

Impaired fertility in women and men with chronic kidney disease.

Chronic kidney disease (CKD) is accompanied by a great number of comorbidities. One of the most clinically important, present in women as well as in men, is infertility. In this review paper, the entire issue of impaired fertility in women and men with CKD is discussed. In both genders, impaired fertility is caused by the interconnection of several factors. In women, these are as follows: the accumulation of uremic toxins; endocrine disorders (e.g., reduced renal clearance of different hormones, disturbed activity of the pituitary-gonadal axis); the impairment of the ovarian function; a reduced ovarian reserve; sexual function disorders; and depression. In men, quite similarly: the accumulation of uremic toxins; endocrine disorders; the impairment of spermatogenesis; direct testicular damage; erectile dysfunction (ED); and depression. The prevalence of impaired fertility increases with the degree of kidney function deterioration in women and men. The highest prevalence of these disturbances is observed in patients with CKD stage 5. Successful kidney transplantation (KTx) in women reduces the accumulation of uremic toxins, restores the function of the endocrine system and improves, but does not normalize, fertility. Similarly in men, KTx restores the function of the endocrine system and improves fertility up to a point, but cannot fully reverse the morphological damage already done to the gonads by the uremia itself. Infertility is one of the important, yet sometimes depreciated complications in women and men with CKD. The etiology and pathogenesis of infertility in CKD is complicated. Kidney transplantation alleviates, but does not fully reverse fertility impairment in CKD patients.

Serum testosterone concentrations in male patients with end-stage kidney disease treated with haemodialysis.

INTRODUCTION: Testosterone deficiency is frequently found in male patients with chronic kidney disease (CKD) and may participate in the pathogenesis of osteoporosis, sarcopaenia, anaemia, impotence, infertility, and other comorbidities observed in these patients. The aim of the study was the evaluation of the frequency of testosterone deficiency in male patients with CKD on maintenance haemodialysis (HD). MATERIAL AND METHODS: In 79 male HD patients, serum total (TT), free (FT) testosterone, C-reactive protein (CRP), and interleukin 6 (IL-6) serum concentrations were assessed before an HD procedure. Patients were divided into three subgroups based on age categories: 19-39 years (18 patients), 40-59 years (34 patients), and ≥ 60 years (27 patients). TT insufficiency and deficiency were diagnosed when the serum TT concentration was below 4.0 ng/mL and 2.9 ng/mL, respectively. FT deficiency was diagnosed in patients with serum FT concentration below 8.9, 6.6, and 4.9 pg/mL in the abovementioned age subgroups, respectively. RESULTS: In the abovementioned age subgroups the serum TT concentration was 5.9 (4.6-7.1), 4.8 (3.9-5.4), and 4.6 (3.9-5.3) ng/mL, respectively. The serum FT concentration was 7.9 (5.2-10.1), 6.1 (5.1-7.2), and 6.0 (5.0-7.1) pg/mL, respectively. In the whole group TT insufficiency was found in 40%, TT deficiency in 15% of patients, and FT deficiency in 50% of patients. Significant negative correlations were found between both serum TT and FT concentrations and age (r = -0.23, p = 0.05 and r = -0.27, p = 0.02, respectively). Additionally, negative correlations were found between both serum TT and FT and IL-6 concentrations (r = -0.43, p < 0.05 and r = -0.29, p < 0.05), respectively. CONCLUSIONS: 1. Testosterone deficiency is common in male patients with chronic kidney disease treated with HD. 2. In HD patients the serum testosterone concentration decreases with age. 3. Chronic inflammation may participate in the pathogenesis of testosterone deficiency in haemodialysis patients.

The Relationship between Initial Tacrolimus Metabolism Rate and Recipients Body Composition in Kidney Transplantation.

There are several premises that the body composition of kidney transplant recipients may play a role in tacrolimus metabolism early after transplantation. The present study aimed at analyzing the relationship between the body composition parameters assessed by bioimpedance analysis (BIA) and initial tacrolimus metabolism. Immediately prior to transplantation, BIA using InBody 770 device was performed in 122 subjects. Tacrolimus concentration-to-dose (C/D) ratio was calculated based on the first blood trough level measurement. There was no difference in phase angle, visceral fat area, lean body mass index (LBMI) and the proportion of lean mass as a percentage of total body mass between the subgroups of slow and fast metabolizers. However, subjects with LBMI ≥ median value of 18.7 kg/m2, despite similar initial tacrolimus dose per kg of body weight, were characterized by a significantly lower tacrolimus C/D ratio (median 1.39 vs. 1.67, respectively; p < 0.05) in comparison with the subgroup of lower LBMI. Multivariate regression analysis confirmed that age (rpartial = 0.322; p < 0.001) and LBMI (rpartial = -0.254; p < 0.01) independently influenced the tacrolimus C/D ratio. A LBMI assessed by BIA may influence the tacrolimus metabolism in the early post-transplant period and can be a useful in the optimization of initial tacrolimus dosing.

Beneficial Effect of Successful Simultaneous Pancreas-Kidney Transplantation on Plasma Profile of Metalloproteinases in Type 1 Diabetes Mellitus Patients.

It is not fully elucidated whether the restoring of normal glucose metabolism after successful simultaneous pancreas-kidney transplantation (SPK) improves vascular wall morphology and function in type 1 diabetic (T1D) patients. Therefore, we compared arterial stiffness, assessed by pulse wave velocity (PWV), carotid intima-media thickness (IMT), and biomarkers of arterial wall calcification in T1D patients after SPK or kidney transplantation alone (KTA). In 39 SPK and 39 KTA adult patients of similar age, PWV, IMT, circulating matrix metalloproteinases (MMPs) and calcification biomarkers were assessed at median 83 months post transplantation. Additionally, carotid plaques were visualized and semi-qualitatively classified. Although PWV and IMT values were similar, the occurrence of atherosclerotic plaques (51.3 vs. 70.3%, p < 0.01) and calcified lesions (35.9 vs. 64.9%, p < 0.05) was lower in SPK patients. There were significantly lower concentrations of MMP-1, MMP-2, MMP-3, and osteocalcin in SPK subjects. Among the analyzed biomarkers, only logMMP-1, logMMP-2, and logMMP-3 concentrations were associated with log HbA1c. Multivariate stepwise backward regression analysis revealed that MMP-1 and MMP-3 variability were explained only by log HbA1c. Normal glucose metabolism achieved by SPK is followed by the favorable profile of circulating matrix metalloproteinases, which may reflect the vasoprotective effect of pancreas transplantation.

Changes in Office Blood Pressure Control, Augmentation Index, and Liver Steatosis in Kidney Transplant Patients after Successful Hepatitis C Infection Treatment with Direct Antiviral Agents.

Hepatitis C virus (HCV) infection in kidney transplant recipients (KTRs) can be successfully treated with direct antiviral agents (DAA). The aim of our study was to analyze different measures of vascular function during and after the DAA treatment. As we have observed the improvement of blood pressure (BP) control in some individuals, we have conducted an analysis of potential explanatory mechanisms behind this finding. Twenty-eight adult KTRs were prospectively evaluated before and 15 months after start of DAA therapy. Attended office BP (OBP), augmentation index (AIx), pulse wave velocity (PWV), flow-mediated dilation (FMD), liver stiffness measurement (LSM), and liver steatosis assessment (controlled attenuation parameter (CAP)) were measured. In half of the patients, improvement of OBP control (decline of systolic BP by at least 20 mmHg or reduction of the number of antihypertensive drugs used) and parallel central aortic pressure parameters, including AIx, was observed. There was a significant decrease in CAP mean values (241 ± 54 vs. 209 ± 30 dB/m, p < 0.05) only in patients with OBP control improvement. Half of our KTRs cohort after successful HCV eradication noted clinically important improvement of both OBP control and central aortic pressure parameters, including AIx. The concomitant decrease of liver steatosis was observed only in the subgroup of patients with improvement of blood pressure control.

Serum sex hormones concentrations in young women in the early period after successful kidney transplantation.

BACKGROUND: Hormonal disorders are frequently present in hemodialysed patients with chronic kidney disease (CKD). In women with CKD sex hormones abnormalities may lead to irregular, often anovulatory cycles, sexual dysfunction and infertility. Kidney transplantation done in young women tends to ameliorate most of the aforementioned disorders and improve fertility. The aim of this study was to assess the changes of serum sex hormones concentration in young women before, and after the first 6 months after successful KTx Material and methods: Fourteen chronic hemodialysis women with CKD undergoing kidney transplantation and 46 apparently healthy women in similar age (control group) were enrolled into the study. In all women serum concentration of: FSH, LH, PRL and estradiol determined. Measurements in the transplanted group were done four times: immediately before surgery, in the 14th - and 30th - day and 6 months after the transplantation. The results are presented as means and 95% CI. RESULTS: All of the women that have finished the study presented an excellent function of the transplanted kidney - mean serum creatinine concentration was 92.54 (74.85 - 110.23) µmol/l. After successful KTx a significant decrease in the serum concentrations of FSH and LH was observed. Decrease of serum PRL concentration after KTx did not reach statistical significance in the multiple comparisons analyses, but returned to the values observed in healthy controls. KTx did not significantly influence serum estradiol concentration. CONCLUSIONS: Successful kidney transplantation leads to the normalization of serum concentrations of hormones linked to fertility disorders in women with chronic kidney disease. < p > < /p >.

Treatment Based on Cinacalcet Reduces Oxidative Stress in Hemodialysis Patients with Secondary Hyperparathyroidism.

BACKGROUND/AIMS: Oxidative stress is one of the leading factors contributing to increased mortality in patients with chronic kidney disease (CKD) and secondary hyperparathyroidism (sHPT). Cinacalcet is now commonly used in the treatment of sHPT in patients with CKD. The aim of this study was to assess the influence of treatment with cinacalcet on the oxidative stress markers in patients on hemodialysis with sHPT. METHODS: In 58 hemodialysed patients with sHPT (parathyroid hormone [PTH] > 300 pg/mL) plasma Advanced Oxidation Protein Products (AOPP), serum total antioxidant capacity - ImAnOx (TAS/TAC), serum PTH, calcium and phosphate concentrations were assessed before the first dose of cinacalcet and after 6 months of treatment. RESULTS: Serum PTH concentration decreased significantly from 895 (748-1,070) to 384 (289-510) pg/mL after 6 months of treatment; p < 0.0001. Mean serum concentrations of -calcium and phosphate remained stable. Plasma AOPP concentration decreased significantly from 152 (126-185) to 49 -(43-57) µmol/L after 6 months of treatment; p < 0.0001. ImAnOx significantly increased from 260 (251-270) to 272 (264-280) µmol/L; p = 0.04. After 6 months of treatment, a significant, positive correlation was found between ImAnOx and the daily dose of cinacalcet (r = 0.30; p = 0.02). Also, the change of serum ImAnOx during treatment with cinacalcet significantly correlated with the daily dose of cinacalcet r = 0.35; p = 0.01. No significant correlations were found between plasma AOPP concentration or ImAnOx and PTH, or their changes in time. CONCLUSIONS: (1) Six-month treatment based on cinacalcet seems to reduce oxidative stress markers in maintenance hemodialysis patients with sHPT. (2) This benefit may be related rather to the direct action of cinacalcet than to the serum PTH concentration decrease.

Arterial stiffness but not endothelial dysfunction is associated with multidrug antihypertensive therapy and nondipper blood pressure pattern in kidney transplant recipients.

Vascular injury related to chronic kidney disease results in increased arterial stiffness and endothelial dysfunction which may affect arterial blood pressure (BP) and influence patient and graft survival in kidney transplant recipients (KTRs).This cross-sectional study aims to elucidate the relationship between the above-mentioned measures of vascular damage and effectiveness of antihypertensive treatment in KTR.One hundred forty-five KTRs 7.6 ±â€Š2.7 years after transplantation were enrolled in our study. Pulse wave velocity (PWV), flow-mediated dilation (FMD), and nitroglycerin-mediated dilation (NMD) were measured, and 24-hour ambulatory BP monitoring was performed.Overall, there were 62 patients with well-controlled or borderline BP and 83 subjects who did not achieve target BP despite antihypertensive treatment. Patients with suboptimal BP control were characterized by greater PWV (median 9.6/interquartile range: 3.9 vs 8.0/3.3 m/s, P = .002), but borderline lower FMD (8.4% ±â€Š5.0% vs 9.9% ±â€Š5.7%; P = .09) as compared with the group with better BP control. When patients were allocated to subgroups based on the number of current antihypertensive medications, no differences in FMD and NMD were found. However, a significant trend was observed for higher PWV values and decreased proportion of dippers along with the increasing number of drugs. PWV, diabetes, and total cholesterol level, but not FMD or NMD, were explanatory variables for systolic BP in multivariate analysis.Arterial stiffness but not endothelial dysfunction is associated with suboptimal BP control in stable KTRs. Less efficient antihypertensive treatment appears to be caused by inadequate control of nocturnal BP.

Fibroblast Growth Factor-23-A Potential Uremic Toxin.

Fibroblast growth factor-23 (FGF23) is a circulating member of the FGF family produced mainly by the osteocytes and osteoblasts that can act as a hormone. The main action of FGF23 is to lower phosphatemia via the reduction of urinary phosphate reabsorption and the decrease of 1,25(OH)2-D generation in the kidney. In the course of chronic kidney disease (CKD), plasma FGF23 concentration rises early, most probably to compensate the inability of the deteriorating kidneys to excrete an adequate amount of phosphate. However, this comes at the cost of FGF23-related target organ toxicity. Results of clinical studies suggest that elevated plasma FGF23 concentration is independently associated with the increased risk of CKD progression, occurrence of cardio-vascular complications, and mortality in different stages of CKD. FGF23 also contributes to cardiomyocyte hypertrophy, vascular calcification, and endothelial dysfunction. The impact of FGF23 on heart muscle is not dependent on Klotho, but rather on the PLCγ-calcineurin-NFAT (nuclear factor of activated T-cells) pathway. Among the factors increasing plasma FGF23 concentration, active vitamin D analogues play a significant role. Additionally, inflammation and iron deficiency can contribute to the increase of plasma FGF23. Among the factors decreasing plasma FGF23, dietary phosphate restriction, some intestinal phosphate binders, cinacalcet (and other calcimimetics), and nicotinamide can be enumerated. Anti-FGF23 antibodies have also recently been developed to inhibit the action of FGF23 in target organs. Still, the best way to normalize plasma FGF23 in maintenance hemodialysis patients is restoring kidney function by successful kidney transplantation.

Endocrine Abnormalities in Patients with Chronic Kidney Disease.

In patients with chronic kidney disease the alterations of the endocrine system may arise from several causes. The kidney is the site of degradation as well as synthesis of many different hormones. Moreover, a number of concomitant pathological conditions such as inflammation, metabolic acidosis and malnutrition may participate in the pathogenesis of endocrine abnormalities in this group of patients. The most pronounced endocrine abnormalities in patients with chronic kidney disease are the deficiencies of: calcitriol, testosterone, insulin-like growth factor and, erythropoietin (EPO). Additionally accumulation of several hormones, such as: prolactin, growth hormone and insulin frequently also occur. The clinical consequences of the abovementioned endocrine abnormalities are among others: anemia, infertility and bone diseases.

Serum parathyroid hormone concentrations measured by chemiluminescence and electrochemiluminescence methods ­ are the results comparable in haemodialysis patients with chronic kidney disease?

INTRODUCTION: Secondary hyperparathyroidism (sHPT) is one of the most common abnormalities found in patients with chronic kidney disease (CKD). Measurement of serum PTH concentrations is crucial in diagnosis and treatment of sHPT. Different methods of serum PTH measurement may provide diverse results. This may have a significant impact on the therapeutic approach if under- or over-diagnosis of sHPT occurs. The aim of this study was to compare the results of serum PTH concentrations measured with two commonly used methods ­ chemiluminescence (CHL) and electrochemiluminescence (ECL). MATERIAL AND METHODS: Seventy-seven haemodialysis patients with CKD were enrolled into the study. Blood samples were collected before haemodialysis, in the middle of the week. In all patients, serum PTH concentrations were measured using two methods: CHL and ECL. RESULTS: Serum PTH concentration measured with CHL was significantly higher than that assessed with ECL: 455 pg/mL (352-559) pg/mL vs. 383 pg/mL (243-523) pg/mL; p < 0.0001. Six patients from the studied cohort were treated with cinacalcet. In these patients, the serum PTH concentration was also significantly higher when measured with CHL than with ECL: 755 pg/mL (294-1216) pg/mL and 607 pg/mL (199-1015 pg/mL); p = 0.027, respectively). In three cases serum PTH concentration assessed with CHL method exceeded 300 pg/mL, whereas when measured with ECL it was below 300 pg/mL. Lower serum PTH concentrations could give the rationale to lower cinacalcet dose or to stop such treatment. CONCLUSIONS: 1. Serum PTH concentrations in haemodialysis patients with CKD measured by CHL and ECL methods differ significantly. 2. The choice of method for measurement of serum PTH concentration in these patients may have important clinical implications.